Angiogenesis, i.e., new blood vessel formation, is essential during embryogenesis and occurs directly after the process vasculogenesis [Gilbert et al. (1997) Developmental biology, Sunderland (MA): Sinauer]. It also plays a critical role in various pathologic disorders including neoplastic [Folkman et al. (1974) Adv Cancer Res 19: 331-58] and certain non-neoplastic diseases such as age-related macular degeneration (AMD), rheumatoid arthritis and diabetic retinopathy [Ohno-Matsui et al. (2001) J Cell Physiol 189: 323-333; Aiello et al. (1994) N Engl J Med 331: 1480-1487; Boulton et al. (1998)Br J Opthalmol 82: 561-568].
Vascular endothelial growth factor (VEGF) is one of the most potent positive regulators in angiogenesis [Ferrara et al. (2004) Endocr Rev 25: 581-611]. Blocking the activity of VEGF derived from tumor cells by specific antibodies suppressed tumor growth in mouse models [Kim et al. (1993) Nature 362: 841-844; Liang et al. (2006) J. Biol. Chem. 281: 951-961]. Bevacizumab, a specific humanized antibody against human VEGF, was approved for treating colorectal cancer patients [Hurwitz et al. (2004) Clin. Colorectal Cancer 4: suppl. 2, S62-S68] and Ranibizumab, a recombinant humanized antibody fragment against human VEGF, was also clinically effective for neovascular AMD patients [Rosenfeld et al. (2006) N Engl J Med 5; 355(14):1419-31]. It is validated that anti-angiogenesis is a successful approach to arrest tumor growth and improve visual acuity in neovascular AMD through blockade of VEGF.